The parent grant "Chronic hypoxia, uterine artery vasoregulation and growth" investigates the mechanisms by which pregnancy and chronic hypoxia influence uterine artery (UA) vasoregulation and growth. Of its three aims, the first two are addressed to experimental animals, using isolated perfused uterine arteries and UA cell culture systems, to determine the effects of pregnancy and chronic hypoxia on vasoregulation, growth, and apoptosis. The third aim involves studies in women residing at 1600 m and 3100 m in Colorado to identify the relationship between serial changes in circulating vasoregulatory and growth factors, UA blood flow, and the clinical outcomes of intrauterine growth restriction (IUGR) and preeclampsia. This FIRCA expands and extends the research of the RO1 to Bolivia, a unique environment (altitudes as high as 4800 m), unique populations (persons of multi-generational high-altitude ancestry and lifelong residents or recent migrants of low-altitude ancestry), and involves more extensive use of novel ultrasound and Doppler technologies. We hypothesize that women of high-altitude, Andean ancestry are protected from altitude-associated intrauterine growth restriction (IUGR) and preeclampsia compared to women of low-altitude, European ancestry residing at similar elevations, as the result of increased uteroplacental O2 delivery. Our specific aims are to compare women of Andean vs. European ancestry living at high altitude to document 1) whether IUGR and preeclampsia are less common in the Andean than European women in conjunction with increased 2) arterial oxygenation, 3) uteroplacental blood flow and, 4) nitrovasodilator relative to endothelin-1 levels. Studies will be conducted using medical records from altitudes ranging from 420 - 4800 m to address aim number 1. Physiological and ultrasound studies will be used to investigate the remaining aims in samples of 40 Andean and 40 European women residents of La Paz, Bolivia at an elevation of 3600 m. These aims are supported by published studies, our preliminary findings concerning birth weight and indices of uteroplacental blood flow in Tibetan high-altitude residents, and by published reports in South Americans. The significance of these studies resides in advancing our knowledge about the mechanisms by which chronic hypoxia alters the uteroplacental vascular response to pregnancy which, in turn, will aid in the identification of improved methods for diagnosis and treatment of IUGR and preeclampsia.